Clinical- and Cost Effectiveness of a Guided Internet-Based Intervention for Children (12–18 Years) of Parents With Mental Disorders (iCHIMPS): Study Protocol of a Multicentered Cluster-Randomized Controlled Trial

Introduction: Children of parents with mental disorders have a high chance of developing a mental disorder themselves. However, this at-risk group is regularly overlooked and typically not seen by any mental health professionals. Internet- and mobile-based interventions (IMIs) can provide a means of promoting mental health for children of parents with mental disorders. Objective: The introduced study will evaluate the clinical- and cost-effectiveness of the iCHIMPS IMI in promoting mental health for children of parents with mental disorders. Methods: A two-armed multicentered cluster-randomized controlled trial (cRCT) comparing the clinical- and cost-effectiveness of the iCHIMPS IMI in the intervention group (IG) to a treatment-as-usual (TAU) control group will be conducted. Recruitment will be handled at currently 21 adult mental health clinics throughout Germany. Participating families will be randomly divided into the two groups until the final sample size of 306 participating adolescents (age 12–18) has been reached. The adolescents in the intervention group will receive access to the IMI and can take part in up to eight intervention modules. Assessment will be conducted during the recruitment (baseline), 1-month, 2-months, and 6-month post-inclusion. Primary outcome is the mental health of the participating adolescents at 6-months post-inclusion as measured by the Youth Self Report score. Secondary self-report outcomes are mental wellbeing, self-efficacy, coping strategies and negative effects as well as mental health of the adolescents as reported by their parent(s). Included moderators are sociodemographic characteristics, working alliance, social support and the mental health diagnoses of the parents. Statistical analyses will be conducted on the intention-to-treat principle as well as with additional per-protocol analyses. Additionally, the cost-effectiveness as well as qualitative data concerning the adherence, acceptance, and feasibility of the IMI will be analyzed. Discussion: The iCHIMPS cRCT examines the clinical- as well as cost-effectiveness of the iCHIMPS mental health promotion IMI for children of parents with mental disorders. This provides the opportunity to gain insights into an innovative as well as time- and location-independent form of support for this often-overlooked at-risk group. Additionally, the larger CHIMPS-NET project allows comparisons between internet-based and face-to-face interventions for a similar target group. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: DRKS00025158. Copyright © 2022 Dülsen, Barck, Daubmann, Höller, Zeidler, Kilian, Wiegand-Grefe and Baumeister

High-frequency oscillations in epilepsy and surgical outcome. A meta-analysis.

High frequency oscillations (HFOs) are estimated as a potential marker for epileptogenicity. Current research strives for valid evidence that these HFOs could aid the delineation of the to-be resected area in patients with refractory epilepsy and improve surgical outcomes. In the present meta-analysis, we evaluated the relation between resection of regions from which HFOs can be detected and outcome after epilepsy surgery.We conducted a systematic review of all studies that related the resection of HFO-generating areas to postsurgical outcome. We related the outcome (seizure freedom) to resection ratio, that is, the ratio between the number of channels on which HFOs were detected and, among these, the number of channels that were inside the resected area. We compared the resection ratio between seizure free and not seizure free patients.In total, 11 studies were included. In 10 studies, ripples (80-200 Hz) were analyzed, and in 7 studies, fast ripples (>200 Hz) were studied. We found comparable differences (dif) and largely overlapping confidence intervals (CI) in resection ratios between outcome groups for ripples (dif=0.18; CI: 0.10-0.27) and fast ripples (dif=0.17; CI: 0.01-0.33). Subgroup analysis showed that automated detection (dif=0.22; CI: 0.03-0.41) was comparable to visual detection (dif=0.17; CI: 0.08-0.27). Considering frequency of HFOs (dif=0.24; CI: 0.09-0.38) was related more strongly to outcome than considering each electrode that was showing HFOs (dif=0.15; CI=0.03-0.27).The effect sizes found in the meta-analysis are small but significant. Automated detection and application of a detection threshold in order to detect channels with a frequent occurrence of HFOs is important to yield a marker that could be useful in presurgical evaluation. In order to compare studies with different methodological approaches, detailed and standardized reporting is warranted

Reliability of EEG Interactions Differs between Measures and Is Specific for Neurological Diseases

Alterations of interaction (connectivity) of the EEG reflect pathological processes in patients with neurologic disorders. Nevertheless, it is questionable whether these patterns are reliable over time in different measures of interaction and whether this reliability of the measures is the same across different patient populations. In order to address this topic we examined 22 patients with mild cognitive impairment, five patients with subjective cognitive complaints, six patients with right-lateralized temporal lobe epilepsy, seven patients with left lateralized temporal lobe epilepsy, and 20 healthy controls. We calculated 14 measures of interaction from two EEG-recordings separated by 2 weeks. In order to characterize test-retest reliability, we correlated these measures for each group and compared the correlations between measures and between groups. We found that both measures of interaction as well as groups differed from each other in terms of reliability. The strongest correlation coefficients were found for spectrum, coherence, and full frequency directed transfer function (average rho > 0.9). In the delta (2–4 Hz) range, reliability was lower for mild cognitive impairment compared to healthy controls and left lateralized temporal lobe epilepsy. In the beta (13–30 Hz), gamma (31–80 Hz), and high gamma (81–125 Hz) frequency ranges we found decreased reliability in subjective cognitive complaints compared to mild cognitive impairment. In the gamma and high gamma range we found increased reliability in left lateralized temporal lobe epilepsy patients compared to healthy controls. Our results emphasize the importance of documenting reliability of measures of interaction, which may vary considerably between measures, but also between patient populations. We suggest that studies claiming clinical usefulness of measures of interaction should provide information on the reliability of the results. In addition, differences between patient groups in reliability of interactions in the EEG indicate the potential of reliability to serve as a new biomarker for pathological memory decline as well as for epilepsy. While the brain concert of information flow is generally variable, high reliability, and thus, low variability may reflect abnormal firing patterns

Distribution of bacterial families within the gut microbiome of <i>Chd1</i> mutant and wild-type flies.

<p>Three sets of filtering parameters were used to analyse the data.</p

Chao1 and Shannon indices of <i>Chd1</i> mutant and wild-type sample replicates.

<p>Three sets of filtering parameters were used to analyse the data.</p

The microbiome composition in the gut of <i>Chd1</i>^<i>-/-</i> and <i>Chd1</i>^<i>WT/WT</i> flies is significantly different.

<p>(A) Principal Coordinate Analysis (PCoA) plot depicting β-diversity by jackknifed UniFrac distances (normalized, weighted UniFrac metric) based on 97% similarity OTU assignments. <i>Chd1</i>^<i>WT/WT</i> and <i>Chd1</i>^<i>-/-</i> replicates differ considerably for PC1, which explains 89.1% of the total variation. To estimate the statistical significance of the clustering a two-sample t-test based on distance matrices (distances within all replicates versus distances between all replicates) was performed (P = 4.709 e-5). (B) Rarefaction curves of 97% identity OTUs for <i>Chd1</i>^<i>WT/WT</i> and <i>Chd1</i>^<i>-/-</i> sample replicates show exhaustive sampling depth.</p

Time-dependent decrease in supplemented <i>L</i>. <i>plantarum</i> in <i>Chd1</i>^<i>-/-</i> but not <i>Chd1</i>^<i>WT/WT</i> flies.

<p>Flies were fed on <i>L</i>. <i>plantarum</i> overnight, transferred to fresh food vials and collected at the indicated days after inoculation. (A) <i>Lactobacillus</i> load was determined by plating fly homogenates on MRS agar; (B) <i>L</i>. <i>plantarum</i> was detected by real-time PCR. Signals were normalized against the <i>Drosophila</i> GAPDH gene and mean values ±SEM of three biological replicates are shown. Significant differences between the two fly lines were analyzed by t-test (level of significance set to p<0.05) and are marked by (*).</p

Age-related changes of bacterial load and species distribution in <i>Chd1</i> mutant and wild-type flies.

<p>(A) Flies of the indicated ages were surface-sterilized and homogenates were plated on Ace agar (left panel) to select for <i>Acetobacteraceae</i> or on MRS agar (right panel) to select for <i>Lactobacillaceae</i>. CFUs per fly were calculated and mean values from four biological replicates ±SEM were plotted. (B) Semiquantitative PCR was used to determine the relative amounts of <i>Acetobacter</i> “A” and <i>Pseudomonas</i> “P” species in guts of flies of the indicated ages. Band intensities were quantified and P/A ratios were calculated. Mean values ±SEM of three biological replicates are shown.</p

Clinical implementation and evaluation of three implementation interventions for a family-oriented care for children of mentally Ill parents (ci-chimps):study protocol for a randomized controlled multicenter trial

BACKGROUND: In Germany, approximately three million children under the age of eighteen have a mentally ill parent. These children are at an increased risk of developing a mental illness themselves (1) as well as a physical illness (2). While research has identified numerous evidence-based family-oriented interventions, little is known about how to implement such interventions effectively and efficiently in clinical practice in Germany. This implementation study (ci-chimps) evaluates three clinical implementation projects with three different implementation interventions for the optimal implementation of the tailored family-oriented preventive and therapeutic interventions in the CHIMPS-NET (children of mentally ill parents—research network) with an implementation model for children of mentally ill parents. METHODS: A two-group randomized controlled multicenter trial will examine changes in family-oriented practice and aspects of implementation at baseline as well as at 12- and 24-months follow-up. The CHIMPS-Network consists of 20 clinical centers. The centers in the intervention group receive the support of all of the three implementation interventions: (1) optimal pathways to care, (2) education and a training program for professionals, and (3) systematic screening for children. The centers in the control group do not receive this specific implementation support. DISCUSSION: While we know that children of mentally ill parents are an important target group to be addressed by preventive and therapeutic interventions, there is often a lack of structured implementation of family-oriented interventions in clinical practice in Germany. Using a randomized controlled multicenter trial design with a large and wide-ranging sample (clinics for adult psychiatry and clinics for child and adolescent psychiatry, university clinics and clinics at the real health care) will provide a robust understanding of implementing family-oriented changes in German clinical practice. TRIAL REGISTRATION: The CHIMPS-NET-study was registered with the German Clinical Trials Register on 2019-12-19 (DRKS00020380) and with Clinical Trials on 2020-4-30 (NCT04369625), the ci-chimps-study was registered with the German Clinical Trials Register (DRKS00026217) on 2021-08-27, the Clinical Trials registration is in review process